The possible role of a perturbed blood-nerve barrier in the pathogenesis of certain diseases of the peripheral nervous system has been suggested but not fully explored. This research program seeks to elucidate the possible roles of a permeable blood-nerve barrier in the pathogenesis of nerve fiber damage in peripheral neuropathies. The recognized components of the blood-nerve barrier, the perineurium's diffusion barrier and the endoneurial capillaries' diffusion barrier, will be studied using the macromolecules horseradish peroxidase and Alcian blue as electron microscopic tracers. The sites and mechanisms of blood-nerve barrier breakdown in lead neuropathy (a neuropathy with primarily segmental demyelination) will be compared with the sites and mechanisms of blood-nerve barrier breakdown in isoniazid neuropathy (a neuropathy with primarily axonal degeneration.) The peripheral nerves of prenatally malnourished rats having a permanently permeable perineurium will be studied by light and electron microscopy to determine the pathological alterations and/or structural adaptations of nerve fibers subjected to a permanently altered blood-nerve barrier. To ascertain whether or not an edema-induced, increased endoneurial pressure can cause nerve-fiber damage, prenatally malnourished rats having a permanently altered perineurium will be intoxicated with either lead or isoniazid. The kind and extent of nerve-fiber damage in these animals having a permeable perineurium (and presumably therefore no increased endoneurial pressure) will be compared with the kind and extent of nerve-fiber damage in animals having an initially intact perineurium (and presumably therefore an edema-induced, increased endoneurial pressure.)